Molecular dynamics simulation of a mixed lipid emulsion model: Influence of the triglycerides on interfacial phospholipid organization

The lipid droplets, in total parenteral nutrition admixtures, are composed of triglycerides surrounded by a phospholipid monolayer. Physicochemical interactions between lipids and the other components are critical for the emulsion stability. To assess these interactions at the molecular level, we have constructed a model of a mixed phospholipid monolayer at the oil-water interface mimicking the lipid droplet surface. Physico-chemical properties of this model are computed by molecular dynamics simulations, and surface pressure-surface area compression isotherms at the air/water interface were recorded in order to compare experimental data to calculated area values. Both phospholipid and triglyceride phases are mixtures close to the composition of the commercial Ivelip® 20% lipid emulsion. In the studied model, the triglyceride phase is formed of 191 triglyceride molecules of four different formulas and each monolayer is composed of 100 molecules of five different zwitterionic or anionic phospholipids. Mixing of different phospholipids has a strong influence on the molecular area and modifies the hydrogen bonding network within the interface. Comparison of the mixed monolayer to a bilayer with the same phospholipid composition demonstrates that the triglycerides play an important role on the interfacial properties of the system. Phospholipid polar headgroups appear more hydrated, molecular area is larger, and lipid tails more disordered in the simulated lipid emulsion model than in the bilayer. The electrostatic potential, however, is the same. Taken together, these results demonstrate the utility of this mixed monolayer model at the oil-water interface instead of a hydrated bilayer model for studying lipid-cations interactions. These simulations are a starting point for further studies where the role of calcium will be analyzed.